Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway

Biomedicine & Pharmacotherapy

Rodrigo Soares Fortunato¹  Raquel Sombra Basílio de Oliveira²  Cleverson Diniz Teixeira de Freitas³  Márcio Viana Ramos³  Andrelina Noronha Coelho-de-Souza⁴  Maria Diana Moreira Gomes⁴  Keciany Alves de Oliveira⁴  Renata Prado Vasconcelos⁴  Adriano César Carneiro Loureiro⁴  Ariclecio Cunha de Oliveira⁴  Ewerton Sousa de Abreu⁴ 

[1] Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av. Pedro Calmon, 550, Rio de Janeiro, Brazil;Centro Universitário Estácio, Fortaleza, Ceará, Brazil;Department of Biochemistry and Molecular Biology, Federal University of Ceará, Av. Humberto Monte, Fortaleza, Brazil;Superior Institute of Biomedical Sciences, State University of Ceará, Av. Silas Munguba, 1700, Fortaleza, Brazil;

关键词: AMPK;    Calotropis;    Glycemia;    Gluconeogenesis;    Latex;    Liver;   

DOI  :  

来源: DOAJ

【 摘 要 】

Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes. In this study the phytomodulatory proteins (LP) from C. procera latex were assessed on glycemic homeostasis.Control animals received a single intravenous dose (5 mg/kg) of LP or saline solution (CTL). Four hours after treatment, the animals were euthanized and their livers were excised for analysis by western blot and RT-PCR AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK) and tumor necrosis factor alpha (TNF-α). In vivo tests of intraperitoneal tolerance to insulin, glucose and pyruvate were also performed, and the effect of LP administration on fed glycemia was studied followed by blood analysis to determine serum insulin levels.Treatment with LP reduced glycemia two hours after glucose administration (LP: 87.2 ± 3.70 mg/dL versus CTL: 115.6 ± 8.73 mg/dL). However, there was no change in insulin secretion (CTL: 14.16 ± 0.68 mUI/mL and LP: 14.96 ± 0.55 mUI/mL). LP improved the insulin sensitivity, represented by a superior glucose decay constant during an insulin tolerance test (kITT) (4.17 ± 0.94%/min) compared to the CTL group (0.82 ± 0.72%/min), and also improved glucose tolerance at 30 min (105.2 ± 12.4 mg/dL versus 154.2 ± 18.51 mg/dL), while it decreased hepatic glucose production at 15 and 30 min (LP: 75.5 ± 9.31 and 52.5 ± 12.05 mg/dL compared to the CTL: 79.0 ± 3.02 and 84.5 ± 7.49 mg/dL). Furthermore, there was a significant inhibition of gene expression of PEPCK (LP: 0.66 ± 0.06 UA and CTL: 1.14 ± 0.22 UA) and an increase of phosphorylated AMPK (LP: 1.342 ± 0.21 UA versus CTL: 0.402 ± 0.09 UA). These findings confirm the effect of LP on glycemic control and suggest LP may be useful in diabetes treatment. However, the pharmacological mechanism of LP in PEPCK modulation still needs more clarification.

【 授权许可】

Unknown